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Subtle heterogeneity of high-affinity choline transporter expression and localization in limbic projections of the cholinergic brainstem tegmentum

机译:高亲和力胆碱转运蛋白在胆碱能脑干被盖的边缘投影中的微弱异质性和定位

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摘要

The high-affinity choline transporter (CHT) supplies the substrate, choline, for the synthesis of acetylcholine (ACh) within cholinergic neurons. Choline uptake mediated by this protein has been studied for over 30 years and many of the regulatory mechanisms governing its function are well characterized. Early studies, as well as more recent investigations, focused on specific populations of cholinergic axons in the brain, namely the cholinergic innervations of cortical, striatal, and hippocampal regions. Details of the expression and subcellular localization of the high-affinity choline transporter within the projections of the pedunculopontine (PPT) and laterodorsal (LDT) tegmental cholinergic neurons have not been examined. The studies described herein compare the cholinergic axons within two limbic regions that are innervated by the ascending projections from these brainstem nuclei. These experiments were designed to characterize: 1) the relative amount and pattern of subcellular localization of the high-affinity choline transporter protein in the axon varicosities of this projection system; 2) the co-expression of the high-affinity choline transporter and the vesicular acetylcholine transporter in these two populations of axon varicosities; and 3) the organization and possible collateralized projections of the cholinergic neurons that provide cholinergic innervation to these regions. The results of these studies indicate that the expression and localization of the high-affinity choline transporter differs only subtly across brain regions innervated by the brainstem tegmental cholinergic neurons, and suggest that these differences may be accounted for by a pattern of specific innervation arising from distinct subsets of pedunculopontine and laterodorsal tegmental cholinergic neurons.
机译:高亲和力胆碱转运蛋白(CHT)为胆碱能神经元内的乙酰胆碱(ACh)合成提供了底物胆碱。已经研究了由这种蛋白质介导的胆碱摄取超过30年,并且已经很好地表征了控制其功能的许多调节机制。早期研究以及更近期的研究都集中在大脑中胆碱能轴突的特定种群,即皮质,纹状体和海马区的胆碱能神经支配。尚未研究高亲和力胆碱转运蛋白在足小脑桥蛋白(PPT)和背嗅(LDT)背盖胆碱能神经元的投射内的表达和亚细胞定位的细节。本文所述的研究比较了两个边缘区域内的胆碱能轴突,这些区域被这些脑干核的上升投射所支配。设计这些实验以表征:1)在该投影系统的轴突静脉曲张中,高亲和力胆碱转运蛋白的亚细胞定位的相对数量和模式; 2)在这两个轴突静脉曲张人群中高亲和力胆碱转运蛋白和水泡乙酰胆碱转运蛋白的共表达; 3)胆碱能神经元的组织结构和可能的侧支投射,可为这些区域提供胆碱能神经支配。这些研究的结果表明,高亲和力胆碱转运蛋白的表达和定位仅在受脑干被盖膜胆碱能神经元支配的大脑区域之间存在细微的差异,并且表明这些差异可能是由不同的特定神经支配模式引起的。 pedunculopontine和晚背盖膜胆碱能神经元的亚群。

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    Holmstrand Ericka C.;

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  • 年度 2011
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